The central hypotheses of this proposal's Research Plan are that detection of cartilage oligomeric matrix protein (COMP) degradative fragments will yield a sensitive and specific marker of arthritis and that the zinc metalloproteinase ADAMTS-7 (ADAMTS = a disintegrin and metalloproteinase with thrombospondin motifs) will be the first physiological enzyme found to be responsible for endogenous COMP degradation in arthritis. To test these hypotheses, the applicant will conduct experiments with the specific aims of (1) determining the potential of COMP fragments as a biomarker of arthritis;(2) characterizing the enzyme(s) and associated endogenous inhibitors responsible for COMP degradation in arthritis;and (3) determining whether the COMP fragment ELISA to be developed is more sensitive and specific than the currently available ELISA in detecting cartilage degeneration in serum from patients with and without arthritis. The applicant has already distinguished himself as a productive scientist. His immediate goal is to improve his knowledge and research skills as they apply to the musculoskeletal system, and his long-term goal is to extend his basic scientific investigations in the service of advancing the diagnosis and treatment of musculoskeletal disorders. The proposal is designed to provide him with new knowledge and experience in the design and management of clinical research studies, allowing him to launch a career as an independent clinical research scientist. The applicant will develop the necessary expertise through a structured career development program under the guidance of mentor Dr. Steven Abramson, a prominent clinician-scientist. Relevance to Public Health: Arthritis eventually afflicts the majority of people, but there is no cure for it. The discovery of biological markers of arthritis promises to bring about dramatic improvement in our ability to treat arthritis, particularly with regard to early diagnosis and institution of treatment before marked loss of joint cartilage has begun.